Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the United States with an estimated 5 million cases annually. Studies have been in progress to define the clinical spectrum of chlamydial infection, to develop improved diagnostic assays and to examine the pathogenesis of chlamydial infection in experimental animal models. Chlamydia infections tend to have the characteristics of a prevalent infection since infection rates vary little by either sex, number of sex partners or the patient's relationship with their sexual partners. Chlamydial cervical infections in women were higher in contacts (26%) than in non-contacts (16%), particularly in contacts of men with gonorrhea (32%), suggesting that co-infection with N. gonorrhoeae and C. trachomatis are quite frequent in this population. Detection of chlamydia species by polymerase chain reaction (PCR) and genotyping by restriction enzyme analysis have been developed. In addition to differentiation of C. pneumoniae, C. trachomatis and C. psittaci, we have demonstrated that nearly three-quarters of C. trachomatis serovars are comprised of D, E and F. Serovar distribution did not correlate with clinical presentation, concurrent gonococcal infection or concordance among sexual couples. In a field study of trachoma in Tanzania, PCR detection of chlamydia genome was demonstrated to have a threefold increase in sensitivity compared to DFA, and a semi-quantitative PCR technique was utilized to monitor response to therapy in over 200 children with trachoma. In an experimental animal model where viability of C. trachomatis can be monitored, we demonstrated persistence of chlamydial DNA by PCR in monkeys who have become culture negative. This persistence of chlamydial DNA may possibly contribute to either a sustained hypersensitivity response or a latent state which is inhibited by the presence of neutralizing antibody and cell - mediated immunity. Finally, the 16s rRNA of C. pneumoniae was sequenced and compared to C. psittaci and C. trachomatis, demonstrating that C. pneumoniae is more closely related to C. psittaci than C. trachomatis. Additional studies utilizing primer sets from the 16s rRNA sequence are planned for PCR detection of C. pneumoniae as an etiologic agent of pneumonia in pediatric, adult and geriatric populations.